BACKGROUND: Microcirculation inflammation (MI, ie: glomerulitis (g) and peritubular capillaritis (ptc)) associated with anti-HLA Donor Specific Antibody (DSA) with or without C4d deposits in ptc currently defines humoral rejection that leads to a poor graft survival. Outcome of isolated MI without DSA and c4d deposit on graft function remains unclear.

METHODS: This multicenter retrospective analysis included 99 patients diagnosed with isolated MI, without DSA, on surveillance biopsies at one year, compared with 251 controls with normal histology and no DSA, with a maximum follow-up of 60 months. DSA were searched by Luminex. MI group had a higher prevalence of non-DSA Classe II anti-HLA antibodies, and depleting induction as compared to control.

MI, interstitial fibrosis and tubular atrophy (IF/TA) score, type of graft (kidney/kidney-pancreas), intertitial inflammation (i) and tubulitis (t), previous acute graft rejection, anti-HLA immunization, and positivity of C4d were included in our multivariate analysis.

RESULTS: Patients with MI had a mean g score of 0.64+/-0.71 and ptc score of 1.49+/-0.84. g+ptc score ≥ 2 was observed in 1/3 of patients. MI was associated with more borderline lesions (45%) as compared to controls (20%, p<0.001). We found more transplant glomerulopathy and IF/TA. Our multivariate model showed that MI was independently associated with a worsening of eGFR decline of -1.9 ml/min/year (p= 0.034). In a subgroup of patients with g+ptc score ≥ 2, decline in eGFR was even higher (-10.16ml/min from 12 to 60 months).

Death and Graft loss was observed in 8% and 4% (MI+) and in 5.6% and 4.5% (controls) respectively, during the follow-up.

CONCLUSION: Isolated Microcirculation Inflammation, on surveillance biopsies at one year, negatively impacts graft function at 3 and 5 years, despite any evidence of anti-HLA DSA humoral activity.

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